Hemostatic compositions in dry storage-stable form that comprise biocompatible, biodegradable, dry stable granular material are known e.g. from WO98/008550A or WO2003/007845A. These products have been successfully applied on the art for hemostasis. Floseal® is an example for a highly effective haemostatic agent consisting of a granular gelatin matrix swollen in a thrombin-containing solution to form a flowable paste.
Since such products have to be applied to humans, it is necessary to provide highest safety standards for quality, storage-stability and sterility of the final products and the components thereof. In addition, manufacturing and handling should be made as convenient and efficient as possible.
A successful product in this field (the Floseal® product mentioned above) utilizes a gelatin matrix used in conjugation with a reconstituted lyophilized thrombin solution. The gelatin matrix is applied as a flowable granular form of gelatin and thrombin with a gelatin content of about 11 to 14.5%. Lower gelatin content results in a runny product with diminished performance due to difficulties in having the product remain at the treatment site, especially under conditions of high blood flow. Higher gelatin particle concentration leads to a product that is difficult to deliver by usual means of administration, such as syringes or catheters, due to higher resistance to flow. The inclusion of plasticizers in the composition, e.g., polyethylene glycols, sorbitol, glycerol, and the like has been suggested (EP0927053B1) and can diminish extrusion force, but inclusion of these materials does not necessarily improve performance.
It is an object of the present invention to provide a hemostatic composition based on a crosslinked gelatin with improved adhering and hemostatic properties compared to the gelatin products such as Floseal according to the prior art and methods for making such hemostatic compositions. The compositions should also be provided in a convenient and usable manner, namely as a flowable paste usable in endoscopic surgery and microsurgery. The products must have an extrusion force of 40 N or below, preferably below 35 N, especially preferred below 20 N. The products should preferably be provided in product formats enabling a convenient provision of “ready-to-use” hemostatic compositions, which can be directly applied to an injury without any time consuming reconstitution steps.